Abstract
BackgroundImmune checkpoints are crucial molecules in maintaining a proper immune balance. Even though age and sex are known to have effects on the immune system, the interplay between age, sex and immune checkpoint expression by T cells is not known. The aim of this study was to determine whether age and sex affect immune checkpoint expression by T cells and if age and sex affect the kinetics of immune checkpoint expression following ex vivo stimulation. In this study, whole blood samples of 20 healthy young adults (YA, 9 males and 11 females) and 20 healthy older adults (OA, 9 males and 11 females) were stained for lymphocyte lineage markers and immune checkpoints and frequencies of CD28+, PD-1+, VISTA+ and CD40L+ T cells were determined. Immune checkpoint expression kinetics were studied following ex vivo anti-CD3/anti-CD28 stimulation of T cells from young and older healthy adults.ResultsWe report an age-associated increase of CD40L + CD4+ and CD40L + CD8+ T-cell frequencies, whereas CD40+ B-cell frequencies were decreased in older adults, suggesting modulation of the CD40L-CD40 interaction with age. Immune checkpoint expression kinetics revealed differences in magnitude between CD4+ and CD8+ T cells independent of age and sex. Further analysis of CD4+ T-cell subsets revealed an age-associated decrease of especially PD-1 + CD4+ memory T cells which tracked with the female sex.ConclusionCollectively, our results demonstrate that both age and sex modulate expression of immune checkpoints by human T cells. These findings may have implications for optimising vaccination and immune checkpoint immunotherapy and move the field towards precision medicine in the management of older patient groups.
Highlights
Immune checkpoints are crucial molecules in maintaining a proper immune balance
Effects of age and sex on numbers of circulating immune cells As ageing has been associated with alterations in peripheral blood immune cell counts, we first determined absolute leukocyte counts in peripheral blood samples of healthy young adults (YA, n = 14) and older adults (OA, n = 14) by TruCount (Fig. 1, Additional Table S1)
Whole blood staining of CD4+ cells in 20 Young adults (YA) and 20 Older adults (OA) employing CD4, CD45RA and CD25 revealed increased ratios of memory over naive T cells in the older group, as OA had a higher frequency of memory CD4+ cells (CD45RA-) than YA (p = 0.028) (Additional Fig. S2A)
Summary
Immune checkpoints are crucial molecules in maintaining a proper immune balance. Even though age and sex are known to have effects on the immune system, the interplay between age, sex and immune checkpoint expression by T cells is not known. Immune checkpoints (ICs) are pivotal molecules in the regulation of the immune response and important when studying age- and sex-associated effects on the immune system. By activating the immune system to boost the immune response to tumour cells, several immunerelated adverse events (irAEs) affecting multiple organs of the body can occur [14]. Among these irAEs, development of rheumatic diseases has been reported [15, 16], which underlines the importance of ICs in inflammatory diseases and adds to the complexity of IC therapy
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